treatment of children cd19+ leukemia and non-hodgkin lymphoma with cd19-tricar-t/silk cell therapy

Conditions: Non-Hodgkin Lymphoma of Intestine; Leukemia

Summary: this is a single arm, open-label, early phase ⅰ study, to determine the safety and efficacy of cd19-tricar-t and cd19-tricar-silk cell therapy in children cd19+ leukemia non-hodgkin lymphoma treatment.

cd19-tricar contains an anti-cd19 scfv, a pd-l1 blocker, and a cytokine complex, enabling the cd19-tricar-t/silk to simultaneously targeting the cd19 positive leukemia or non-hodgkin lymphoma，blocking the inhibitory pd-l1 signal and stimulating innate t/nk cell activation and expansion, thus make it a tri- functional car (tri-car). cd19-tricar-t is an autologous tri-functional car-t cell therapy, cd19-tricar-silk is an allogeneic tri-functional car- nk cell therapy, patients ineligible for leukapheresis or car-t therapy will be recommended for cd19-tricar-silk therapy.

Eligibility criteria:
inclusion criteria: for children cd19 positive b cell leukemia： 1. all subjects must personally sign and date the informed consent before initiating any study specific procedures or activities; 2. all subjects must be able to comply with all the scheduled procedures in the study; 3. cd19-positive b-cell leukemia with histology or cytology confirmed recurrence after treatment; or progression during treatment; or after first line treatment getting a mrd negative, 2 times of mrd show\>0.01% but without bone marrow morphology recurrence; 4. at least one measurable lesion; 5. aged \<18 years; or diagnosised at the age of less than 18 and relapsed within three years， determined by the investigator; 6. expected survival ≥12 weeks; 7. eastern cooperative oncology group(ecog) performance status of≤2; 8. before cd19-tricar-t/silk cell infusion, systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks; 9. all other treatment induced adverse events must have been resolved to ≤grade 1; for children cd19 positive b cell lymphoma： 1. all subjects must personally sign and date the informed consent before initiating any study specific procedures or activities; 2. all subjects must be able to comply with all the scheduled procedures in the study; 3. cd19-positive b-cell lymphoma with histology or cytology confirmed recurrence after treatment，defined as one or more of the following: disease progression during standard therapy；recurrence after termination of treatment；relapse after autologous hematopoietic stem cell transplantation；not suitable for stem cell transplantation or abandon stem cell transplantation due to conditional restrictions; 4. at least one measurable lesion; 5. aged \<18 years; or diagnosised at the age of less than 18 and relapsed within three years， determined by the investigator; 6. expected survival ≥12 weeks; 7. eastern cooperative oncology group(ecog) performance status of≤2; 8. before cd19-tricar-t/silk cell infusion, systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks; 9. all other treatment induced adverse events must have been resolved to ≤grade 1; exclusion criteria: 1. presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring iv antimicrobials for management. (simple uti and uncomplicated bacterial pharyngitis are permitted if responding to active treatment); 2. patients with symptomatic central nervous system metastasis, intracranial metastasis, and cancer cells found in cerebrospinal fluid are not recommended to participate in this study. symptom free or post-treatment stable disease or disappearance of lesions should not be excluded. the specific selection is ultimately determined by the investigator; 3. lactating women or women of childbearing age who plan to conceive during the time period; 4. active infection with hepatitis b (hbsag positive) or hepatitis c virus (anti-hcv positive); 5. known history of infection with hiv; 6. subjects need systematic usage of corticosteroid; 7. subjects need systematic usage of immunosuppressive drug; 8. planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study; 9. other reasons the investigator consider the patient may not be suitable for the study.

Keywords: non-hodgkin lymphoma leukemia children cd19 car-t tricar-t tricar-silk